Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS)
Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS)
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DOI：
10.1002/term.2206
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发表时间：
2017-11-01
影响因子：
3.3
通讯作者：
Humes, H. David
中科院分区：
文献类型：
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作者：
Johnston, Kimberly A.;Westover, Angela J.;Humes, H. David
细胞疗法在急性肾功能衰竭中的治疗已被证明是成功的，具有治疗作用，但用于治疗慢性肾功能衰竭的可持续的、可移植的生物人工肾的开发尚未实现。维持抗凝血液循环是清除溶质和支持生物成分的典型平台，这是这项技术进步的主要障碍。该小组开发了一种生物人工肾上皮细胞系统(BRECS)，能够在血液以外的体液支持下分化肾细胞功能。为了评估这种装置在终末期肾脏疾病中的潜在应用，建立了一个大型动物模型，利用腹膜透析液支持生物装置并提供细胞治疗，同时提供尿毒症控制。肾绵羊接受了包括BRECS在内的连续流腹膜透析(CFPD)循环。绵羊接受含有1×10(8)肾上皮细胞的BRECS或去细胞假装置处理长达7天。体外腹腔液循环维持BRECS细胞活性和活性。观察到BRECS治疗的系统免疫学效果，因为细胞处理的绵羊比假处理的绵羊更好地保留了中性粒细胞的氧化活性。这一模型表明，在CFPD电路中使用BRECS体现了一种可持续和有效的可穿戴生物人工肾的可行方法。版权所有(C)2016 John Wiley&Sons，Ltd.
Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 x 10(8) renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright (c) 2016 John Wiley & Sons, Ltd.